Viral diseases of the lymphoid system

• What is immunocompromised?

  Any aspect of the host defences is deficient, impaired or weakened immune system.
• What is immunosuppresed?

  Immune defences are specifically impaired, reduction in immune system.
• Interaction of a virus with a cell

  Virus infects the cell, can get non-productive or productive interaction leading to either viral destruction or latent infection.

  Non-productive infection leads to viral destruction, latent infection or oncogenic transformation (the virus inserts itself into the cell and starts changing things, stimulates tumour production).

  Productive infection leads to lytic infection (cell dies and releases a lot of infection) or persistent infection (balance in the body, virus is in and out.
• How does a virus enter a cell?

  Utilisation of naturally occurring and useful receptors on the cell surface.

  Endocytosis: both enveloped and non-enveloped viruses.

  Direct injection (bacteriophages).

  Fusion of the envelope (some enveloped viruses).
• Haematopoiesis

  The type of cells affected will depend on stage of the cascade when the progenitor cells were affected.

  
• Canine distemper virus

  Morbillivirus related to measles, RNA enveloped virus (poor survival in the environment).

  Infects a number of cells but has particular ‘tropism’ for lymphocytes (causes there destruction).

  Oro-nasal infection (inhalation of aerosol) - replication in local lymphoid tissue-macrophages-dessimation to local lymph nodes spreads to other organs (spleen, bone marrow).
• Canine parvovirus 2 and feline panleukopenia virus

  CPV and FPV.

  Non-enveloped DNA virus.

  Tropism for fast dividing cells (gastrointestinal tract-crypts, bone marrow, lymphoid tissue).

  Destruction of white blood cells precursors within bone marrow, sequestration of neutrophils with GI tract, damage to the barrier leading to bacterial translocation.
• Feline leukaemia virus (FeLV).

  Retrovirus, RNA virus, Oncovirus family, worldwide distribution.

  Affects lymphocytes - causes leukaemia (in the blood, start of the disease in the bone marrow), and lymphoma (tumour starts in lymph nodes and starts spreading) in cats.

  Retrovirus - have to translate themselves back to DNA to create new viruses - can incorporate themselves into DNA and cause tumours. Can mutate quite easily.

  Can be transmitted from mom to kitten - not always though.
• Pathogenesis of FeLV infection.

  Mouth and nose contact with virus-containing saliva - replication in the draining lymph nodes -

  • Lymphoid tissue - peripheral blood, leukocytes.
  • Bone marrow - peripheral blood, leukocytes, platelets.

  Epithelial cells - saliva, nasal secretion and urine circling back to contamination via nose to nose contact. Can be spread via litter trays, bowls, bite wounds and mutual grooming.
• What is abortive infection?

  Animal picked up the virus and fought it off, so you can’t see any signs of infection, will test negative.
• What is regressive infection?

  The animal does have the virus but is keeping it at bay, stopping it form replicating, can test positive or negative depending on sensitivity of the test and effectiveness of the animals immune system.
• What is progressive infection?

  Animals can’t suppress the virus anymore and it starts replicating, leading to shedding and infection of other animals.
• Pathophysiology of FeLV

  Each cat can present differently.

  Much more severe and less selective than FIV (lymphopenia, neutropenia, impaired neutrophil function, loss of CD4 and CD8 cells).

  Anameia; regenerative (usually through secondary causes e.g. Mycoplasma haemofelis or immune mediated destruction) or non-regenerative (direct effect of the virus on bone marrow).

  Neoplasia (lymphoma and leukaemia) though these days are uncommonly associated.
• Feline immunodeficiency virus

  Retrovirus, RNA virus, Lentivirus genus
• Feline immunodeficiency virus

  • Infects CD4+ T lymphocytes which are crucial for humoral and cell-mediated immunity
  • Invades dendritic cells, macrophages and CD4+ T-cells
  • Can be detected in circulation, slow increase in viral particles and proviral DNA up to 12 weeks
  • Seroconversion within 2-4 weeks
  • Decrease in viral loads - entering asymptomatic phase
  • Latency - protection from immune system
  • Functional immunodeficiency through decline of CD4+ cells leads to AIDS-like deterioration
  • Late in the disease, antibodies level may decline and animal may test negative
• Feline infectious peritonitis virus (FIP)

  Enveloped RNA virus. FCoV - enteric virus, ubiquitous in the feline population.

  2 forms: effusive (‘wet FIP’) and non-effusive (‘dry’ FIP).

  Only a small proportion of cats will develop FIP, biphasic peak.

  Mutation that allows the virus to infect monocytes is the key part of the FIP pathophysiology.

  Presence of antibodies is not diagnostic of FIP.
• Pathophysiology of FIP virus

  Activated monocytes express cytokines and adhesion molecules which facilitate interactions with small-medium veins.

  Endothelial barrier dysfunction - extravasation of monocytes - increased vascular permeability leading to effusions.

  Antibody dependant enhancement (ADE) = potential for exacerbation of the disease by pre-existing antibodies